Metformin treatment of high-fat diet-fed obese male mice restores sperm function and fetal growth,without requiring weight loss  

作　　者：Nicole O McPherson Michelle Lane 

机构地区：[1]Robinson Research Institute,School of Medicine,University of Adelaide,Adelaide 5005,Australia [2]Freemasons Foundation Centre for Men's Health,University of Adelaide,Adelaide 5005,Australia [3]Repromed,Dulwich 5065,Australia [4]Monash IVF Group,Melbourne 3000,Australia.

出　　处：《Asian Journal of Andrology》2020年第6期560-568,共9页亚洲男性学杂志（英文版）

摘　　要：Male obesity is associated with subfertility and increased disease risk of offspring.It is unknown if effects can be reversed through pharmacological interventions.Five-to 6-week-old C57BL6 male mice were fed control diet(n=10,CD)or high-fat diet(n=20,HFD)for 16 weeks.Animals fed with a HFD were then allocated to continuation of HFD(n=8)or HFD with metformin 28 mg kg1 day-1(n=8)for 6 weeks.Animals fed with CD continued on a CD(n=9).Males were mated with fertile C57BL6 females for the assessment of pregnancy and fetal growth.Sperm motility,spermatozoa and testicular morphology,sperm-zona pellucida binding,sperm reactive oxygen species(ROS)(intracellular[DCFDA],superoxide[MSR],and oxidative DNA lesions[8OHdG]),and mitochondrial membrane potential(JC1)were assessed.Metformin treatment of HFD males improved glucose toleranee(+12%,P<0.05)and reduced Homeostatic Model Assessment of Insulin Resistance(HOMA-IR;-36%,P<0.05).This occurred in the absenee of a change in body weight or adiposity.Metformin treatment of HFD-fed males restored testicular morphology(+33%,P<0.05),sperm motility(+66%,P<0.05),sperm-zona pellucida binding(+25%,P<0.05),sperm intracellular ROS concentrations(-32%,P<0.05),and oxidative DNA lesions(-45%,P<0.05)to the levels of the CD males.Metformin treatment of HFD fathers increased fetal weights and lengths compared with those born to HFD fathers(+8%,P<0.05),with fetal lengths restored to those of fetuses of CD males.Short-term metformin treatment in men who are obese could be a potential intervention for the treatment of subfertility,without the need for a reduction in body weight/adiposity.

关 键 词：FERTILITY glucose metabolic syndrome OVERWEIGHT SUBFERTILITY 

分 类 号：R698.2[医药卫生—泌尿科学]